Calibration of In Vitro Multidrug Resistance Protein 1 Substrate and Inhibition Assays as a Basis to Support the Prediction of Clinically Relevant Interactions In Vivo

2014 ◽  
Vol 42 (9) ◽  
pp. 1411-1422 ◽  
Author(s):  
Agnès Poirier ◽  
Anne-Christine Cascais ◽  
Urs Bader ◽  
Renée Portmann ◽  
Marie-Elise Brun ◽  
...  
2016 ◽  
Vol 76 ◽  
pp. 11-17 ◽  
Author(s):  
Flavia Temperilli ◽  
Manuela Di Franco ◽  
Isabella Massimi ◽  
Maria Luisa Guarino ◽  
Maria Paola Guzzo ◽  
...  

2014 ◽  
Vol 737 ◽  
pp. 159-167 ◽  
Author(s):  
Li-Ming Lien ◽  
Zhih-Cherng Chen ◽  
Chi-Li Chung ◽  
Ting-Lin Yen ◽  
Hou-Chang Chiu ◽  
...  

2014 ◽  
Vol 58 (12) ◽  
pp. 7390-7397 ◽  
Author(s):  
Maria Isabel Veiga ◽  
Nuno S. Osório ◽  
Pedro Eduardo Ferreira ◽  
Oscar Franzén ◽  
Sabina Dahlstrom ◽  
...  

ABSTRACTPlasmodium falciparumhas the capacity to escape the actions of essentially all antimalarial drugs. ATP-binding cassette (ABC) transporter proteins are known to cause multidrug resistance in a large range of organisms, including theApicomplexaparasites.P. falciparumgenome analysis has revealed two genes coding for the multidrug resistance protein (MRP) type of ABC transporters:Pfmrp1, previously associated with decreased parasite drug susceptibility, and the poorly studiedPfmrp2. The role ofPfmrp2polymorphisms in modulating sensitivity to antimalarial drugs has not been established. We herein report a comprehensive account of thePfmrp2genetic variability in 46 isolates from Thailand. A notably high frequency of 2.8 single nucleotide polymorphisms (SNPs)/kb was identified for this gene, including some novel SNPs. Additionally, we found thatPfmrp2harbors a significant number of microindels, some previously not reported. We also investigated the potential association of the identifiedPfmrp2polymorphisms with alteredin vitrosusceptibility to several antimalarials used in artemisinin-based combination therapy and with parasite clearance time. Association analysis suggestedPfmrp2polymorphisms modulate the parasite'sin vitroresponse to quinoline antimalarials, including chloroquine, piperaquine, and mefloquine, and association within vivoparasite clearance. In conclusion, our study reveals that thePfmrp2gene is the most diverse ABC transporter known inP. falciparumwith a potential role in antimalarial drug resistance.


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